Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals?

Yvette C. Wong; Kelvin Luk; Kerry Purtell; Samuel Burke Nanni; A. Jon Stoessl; Louis Eric Trudeau; Zhenyu Yue; Dimitri Krainc; Wolfgang Oertel; Jose A. Obeso; Laura A. Volpicelli-Daley

doi:10.1002/mds.27823

Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals?

Yvette C. Wong, Kelvin Luk, Kerry Purtell, Samuel Burke Nanni, A. Jon Stoessl, Louis Eric Trudeau, Zhenyu Yue, Dimitri Krainc, Wolfgang Oertel, Jose A. Obeso^*, Laura A. Volpicelli-Daley

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Review article › peer-review

66 Scopus citations

Abstract

While current effective therapies are available for the symptomatic control of PD, treatments to halt the progressive neurodegeneration still do not exist. Loss of dopamine neurons in the SNc and dopamine terminals in the striatum drive the motor features of PD. Multiple lines of research point to several pathways which may contribute to dopaminergic neurodegeneration. These pathways include extensive axonal arborization, mitochondrial dysfunction, dopamine's biochemical properties, abnormal protein accumulation of α-synuclein, defective autophagy and lysosomal degradation, and synaptic impairment. Thus, understanding the essential features and mechanisms of dopaminergic neuronal vulnerability is a major scientific challenge and highlights an outstanding need for fostering effective therapies against neurodegeneration in PD. This article, which arose from the Movement Disorders 2018 Conference, discusses and reviews the possible mechanisms underlying neuronal vulnerability and potential therapeutic approaches in PD.

Original language	English (US)
Pages (from-to)	1406-1422
Number of pages	17
Journal	Movement Disorders
Volume	34
Issue number	10
DOIs	https://doi.org/10.1002/mds.27823
State	Published - Oct 1 2019

Funding

Y.C.W.: NIH: K99NS109252. K.L.: NIH/NINDS: R01NS088322. S.B.N.: Parkinson Canada graduate fellowship. L.-E.T.: Canadian Institutes of Health Research, the Brain Canada and Krembli Foundations, and Parkinson Canada. Z.Y.: NIH/NINDS: P50NS0947331 and R01NS060123. D.K.: NIH/NIA: R01NS076054 and NIH/NINDS: R01NS096240. W.O.: Charitable Hertie Foundation, ParkinsonFonds Deutschland. J.O.: Fundación BBVA; Obra Social Fundación “La Caixa”); Plan Nacional: Ministerio de Economía y Competitividad: SAF2015-67239-P Ciberned. L.V.-D.: NIH/NINDS: R01NS102257, P50 NS108675, Michael J. Fox Foundation. Dominantly inherited mutations in SCNA/PARK4, which encodes α-syn, the major component in LBs, was the first identified genetic cause for PD. Normally, the majority of α-syn concentrates at presynaptic terminals where it associates with synaptic vesicles.

Keywords

Parkinson
dopamine
substantia nigra
synaptic
synuclein

ASJC Scopus subject areas

Clinical Neurology
Neurology

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10.1002/mds.27823

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title = "Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals?",

abstract = "While current effective therapies are available for the symptomatic control of PD, treatments to halt the progressive neurodegeneration still do not exist. Loss of dopamine neurons in the SNc and dopamine terminals in the striatum drive the motor features of PD. Multiple lines of research point to several pathways which may contribute to dopaminergic neurodegeneration. These pathways include extensive axonal arborization, mitochondrial dysfunction, dopamine's biochemical properties, abnormal protein accumulation of α-synuclein, defective autophagy and lysosomal degradation, and synaptic impairment. Thus, understanding the essential features and mechanisms of dopaminergic neuronal vulnerability is a major scientific challenge and highlights an outstanding need for fostering effective therapies against neurodegeneration in PD. This article, which arose from the Movement Disorders 2018 Conference, discusses and reviews the possible mechanisms underlying neuronal vulnerability and potential therapeutic approaches in PD.",

keywords = "Parkinson, dopamine, substantia nigra, synaptic, synuclein",

author = "Wong, {Yvette C.} and Kelvin Luk and Kerry Purtell and {Burke Nanni}, Samuel and Stoessl, {A. Jon} and Trudeau, {Louis Eric} and Zhenyu Yue and Dimitri Krainc and Wolfgang Oertel and Obeso, {Jose A.} and Volpicelli-Daley, {Laura A.}",

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doi = "10.1002/mds.27823",

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T2 - Should the focus be on axons and synaptic terminals?

AU - Wong, Yvette C.

AU - Luk, Kelvin

AU - Purtell, Kerry

AU - Burke Nanni, Samuel

AU - Stoessl, A. Jon

AU - Trudeau, Louis Eric

AU - Yue, Zhenyu

AU - Krainc, Dimitri

AU - Oertel, Wolfgang

AU - Obeso, Jose A.

AU - Volpicelli-Daley, Laura A.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - While current effective therapies are available for the symptomatic control of PD, treatments to halt the progressive neurodegeneration still do not exist. Loss of dopamine neurons in the SNc and dopamine terminals in the striatum drive the motor features of PD. Multiple lines of research point to several pathways which may contribute to dopaminergic neurodegeneration. These pathways include extensive axonal arborization, mitochondrial dysfunction, dopamine's biochemical properties, abnormal protein accumulation of α-synuclein, defective autophagy and lysosomal degradation, and synaptic impairment. Thus, understanding the essential features and mechanisms of dopaminergic neuronal vulnerability is a major scientific challenge and highlights an outstanding need for fostering effective therapies against neurodegeneration in PD. This article, which arose from the Movement Disorders 2018 Conference, discusses and reviews the possible mechanisms underlying neuronal vulnerability and potential therapeutic approaches in PD.

AB - While current effective therapies are available for the symptomatic control of PD, treatments to halt the progressive neurodegeneration still do not exist. Loss of dopamine neurons in the SNc and dopamine terminals in the striatum drive the motor features of PD. Multiple lines of research point to several pathways which may contribute to dopaminergic neurodegeneration. These pathways include extensive axonal arborization, mitochondrial dysfunction, dopamine's biochemical properties, abnormal protein accumulation of α-synuclein, defective autophagy and lysosomal degradation, and synaptic impairment. Thus, understanding the essential features and mechanisms of dopaminergic neuronal vulnerability is a major scientific challenge and highlights an outstanding need for fostering effective therapies against neurodegeneration in PD. This article, which arose from the Movement Disorders 2018 Conference, discusses and reviews the possible mechanisms underlying neuronal vulnerability and potential therapeutic approaches in PD.

KW - Parkinson

KW - dopamine

KW - substantia nigra

KW - synaptic

KW - synuclein

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JO - Movement Disorders

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Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals?

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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